The Center for Macromolecular Modeling and Bioinformatics develops software tools to model cellular processes in atomic detail. An experienced, multidisciplinary team of researchers at the Center provides for the biomedical research community a computational microscope equipped with molecular visualization, sequence, structure and dynamics analysis, and collaborates with leading experimental laboratories. The Center will expand the use of its computational tools to a broad range of biomedical research problems and provide easy access to these tools for the biomedical research community. In the next funding period, the Center will pursue the following specific aims: Raise performance, efficiency, and accuracy of simulations for cellular processes. Facilitate innovation in the biomedical research community by providing accessible simulation tools supporting, in particular, enhanced sampling, coarse-grained models, and quantum effects; Support visualization and analysis of biomolecular systems with powerful, customizable software packages, integrating multi-modal structure viewing and analysis with model building and simulation tools; Enhance performance for visualization, analysis, and modeling of large size and long timescale cellular processes by exploiting emerging technologies such as graphics processor accelerators and solid state disks; Develop methods to model large cellular domains such as membrane environments; improve tools for structure prediction and refinement, e.g., for large, flexible protein-RNA assemblies. Scale coarse-grained simulation methods to eukaryotic-sized cells; Drive the development of novel computational tools and methods through collaborations with both theoretical and experimental laboratories; Enhance service, training, and dissemination, providing a cutting edge computational laboratory, hands-on training, first-rate educational material, and an extensive, widely-used website to biomedical researchers.